Target genes of LIN-12/Notch signaling in vulval precursor cells in Caenorhabditis elegans.

摘要

The C. elegans vulva is an important paradigm for cell-cell interactions in animal development. The fates of six vulval precursor cells are patterned through the action of the EGFR-MAPK inductive signaling pathway, which specifies the "1°" fate, and the LIN-12/Notch lateral signaling pathway, which specifies the "2°" fate.; We provide evidence that the inductive signal is spatially graded and initially activates the EGFR-MAPK pathway in the prospective 2° cells. Subsequently, this effect is counteracted by the expression of multiple new negative regulators of the EGFR-MAPK pathway, under direct transcriptional control of the LIN-12-mediated lateral signal.; We also identify a microRNA gene, mir-61, as a direct transcriptional target of LIN-12, and show that expression of mir-61 promotes the 2° fate. We identify vav-1, the ortholog of the Vav oncogene, as a target of mir-61, and show that downregulation of VAV-1 promotes lin-12 activity in specifying the 2° fate. Our results suggest that lin-12, mir-61 and vav-1 form a feedback loop that helps maximize lin-12 activity in the presumptive 2° VPCs.